The FDA has approved epoetin alfa-epbx (Retacrit) as a biosimilar to epoetin alfa (Epogen/Procrit) for the treatment of anemia caused by chemotherapy, chronic kidney disease, or use of zidovudine in patients with HIV infection.
The indication also included use of epoetin alfa-epbx before and after surgery to reduce the likelihood that patients will need a red blood cell transfusion due to blood loss from surgery.
“It is important for patients to have access to safe, effective, and affordable biological products and we are committed to facilitating the development and approval of biosimilar and interchangeable products,” Leah Christl, PhD, director of the Therapeutic Biologics and Biosimilars Staff in the FDA’s Center for Drug Evaluation and Research, said in a statement.
This is the first oncology-related biosimilar approved since President Trump announced his ‘blueprint’ for reducing the costs of drugs
in the US last week.
“Biosimilars can provide greater access to treatment options for patients, increasing competition and potentially lowering costs,” Christl said.
The Path to Approval
In May 2017, the FDA’s Oncologic Drugs Advisory Committee voted 14 to 1 recommending approval of a biologics license application (BLA) for epoetin alfa-epbx.
At the time, the committee noted that, “The totality of the analytical similarity data supports the conclusion that epoetin [alfa-epbx] is highly similar to US-licensed Epogen/Procrit, notwithstanding minor differences in clinically inactive components. The clinical data, including pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety and immunogenicity data support a finding of no clinically relevant differences.”
Hospira, the manufacturer of epoetin alfa-epbx, submitted the application based on results from 2 single-center, randomized, open-label studies, EPOE-12-02 and EPOE-14-01. The first was aimed to establish the PK and PD (reticulocyte count) of epoetin alfa-epbx following a single subcutaneous dose of 100 u/kg in healthy participants (N = 81). EPOE-14-01 was designed to determine the drug’s PK and PD (hemoglobin level) following multiple doses of subcutaneous 100 u/kg epoetin alfa-epbx 3 times weekly for 4 weeks in healthy participants (N = 129). Epoetin alfa-epbx was compared with epoetin alfa in both studies.
In EPOE-12-02, researchers found that epoetin alfa-epbx met the prespecified acceptance criteria for PK similarity, the geometric mean of AUC0-INF (1.06 mIU-h/mL; 90% CI, 1.01-1.11), AUC0-T (1.03 mIU-h/mL; 90% CI, 0.97-1.09), and CMAX
(1.09 mIU-h/mL; 90% CI, 1.01, 1.18). The same was true of PD for AUEC0-456 (1.01%-h; 90% CI, 0.98-1.05) and EMAX
(1.02%-h; 90% CI, 0.99-1.05).
In EPOE-14-01, epoetin alfa-epbx also met prespecified acceptance criteria for PD similarity of geometric mean of hemoglobin level AEUC 0-28d (1.00 g-h/dL; 90% CI, 0.99-1.02) and EMAX
(1.00 g/dL; 90% CI, 0.99-1.02).
In June 2017, the FDA issued a complete response letter to Hospira for epoetin alfa-epbx, citing manufacturing concerns at the company’s fill-finish facility in McPherson, Kansas. Pfizer, Hospira’s parent company, announced the agency’s decision in a press release on June 22. 2017.
The FDA sent a warning letter to Pfizer dated February 14, 2017, detailing 5 areas of concern, including in-process specifications, failure to follow procedures to prevent microbiological contamination of drug products, and a lack of “scientifically sound and appropriate sampling plans for inspection and analytical activities.”
The agency argued that the company should have known the McPherson site might have problems because the FDA cited 5 other Hospira plants for similar problems from 2010 to 2015.
“These repeated failures at multiple sites demonstrate that your company’s oversight and control over the manufacture of drugs is inadequate,” the letter explained.
Pfizer stressed that none of those issues specifically related to epoetin alfa-epbx, though the McPherson plant was a potential manufacturing site. The company added that FDA did not request more data to support a further approval, as it did in 2015, when the agency rejected an abbreviated BLA.
In its statement in June 2017 regarding the complete response letter, Pfizer reported that the company had submitted a corrective and preventative action plan to the FDA in March 2017 and was working to address the concerns listed in the warning letter. Today’s approval indicates that the FDA was satisfied with the company’s actions.